The long range goal of this proposal is to evaluate the allophenic mouse as a model to study cellular aging in the immune system. Allophenic mice will be constructed so that cells from a short-lived mouse strain and a long-lived mouse strain are combined to give a single chimeric animal. The peripheral blood lymphocytes will be isolated from these animals at two month intervals during the course of their lives. The parental strain origin of the lymphocytes will be determined using external markers (H-2 antigens) and internal markers (enzyme polymorphisms). At each time point the population of lymphocytes will be analyzed for the relative proportions of the two types of parental cells. In the environment of the allophenic mouse the lymphocytes from the short-lived strain could die earlier, at the same time, or later than the lymphocytes from a normal short-lived control animal. Likewise, the lymphocytes from the long-lived strain could die earlier, at the same time, or later than the lymphocytes from a normal long-lived control animal. As the allophenic animals age, we will assay for possible changes in the expression of H-2 antigens and enzyme polymorphisms in the lymphocytes, as well as for the presence or absence of the two parental cell types. We hope to use the controlled environment of the allophenic mouse to assess the relative contributions of genotype and environment to lymphocyte longevity and integrity.